Scientists find new protein key to bowel disease

LONDON (Reuters) - Using drugs or diet to boost a protein to restore the body's natural defences to gut infections may offer a new way to treat currently incurable bowel diseases such as Crohn's disease, European scientists said on Monday based on a study using mice.

Researchers led by scientists from the Pasteur Institute in Lille, France used mice engineered to be low in a protein called PPAR-gamma, which regulates defences that kill bacteria in the gut, and found they were less able to fight off bacterial infection in the colon compared to normal mice.

The European team, whose work was published in the Proceedings of the National Academy of Sciences (PNAS) journal, found that samples taken from the colons of humans diagnosed with Crohn's disease also show reduced levels of the antimicrobial peptides, or defences, regulated by the PPAR-gamma protein.

Inflammatory bowel conditions such as Crohn's disease and ulcerative colitis affect around 0.5 percent of the population in developed nations and are notoriously difficult to treat.

Treatments include surgery as well as a group of injectable drugs that block an inflammatory protein called tumour necrosis factor (TNF) such as Johnson & Johnson's Remicade, Abbott's Humira and UCB's Cimzia, but Mathias Chamaillard said not all patients respond to these, and others find they stop being effective after time.

Chamaillard, who led the study, said in a telephone interview the results showed that drugs already used for other diseases could prove effective in Crohn's disease.

For example, GlaxoSmithKline's diabetes drug Avandia, known generically as rosiglitazone, has been shown to restore gut defences through PPAR-gamma activation, he said, and Takeda Pharmaceutical's Actos, or pioglitazone, another PPAR drug used in diabetes, acts in the same way.

Still, although the study involved human tissue samples, many findings in mice do not pan out in humans.

Chamaillard said foods or diets containing conjugated linoleic acid (CLA) can also boost PPAR-gamma activity and have been shown to improve colitis and colitis-associated cancer. CLA is primarily found in milk and meat products.

"In the short-term, managing the disease is what we are looking at, but it may also be that in the future we could develop a way of stopping it," Chamaillard said.

But he added that curing Crohn's disease would mean being able to identify those at highest risk before they contracted it and then being able to boost PPAR gamma-related defences to ward it off -- both areas that would need more research.

SOURCE: Proceedings of the National Academy of Sciences, online April 26, 2010.